Delirium is a major challenge facing geriatric practice due to its prevalence, complex etiology, and potential severe impact on patients. Postoperative delirium is associated with longer hospital stays, poor functional outcomes, and higher healthcare costs. A milder form of acute cognitive change known as postoperative cognitive decline (POCD) is associated with long term declines in daily functioning. Despite the prevalence and clinical importance of postoperative delirium and POCD, a preventive therapy has not been identified. Patients' risk for the development of geriatric syndromes (such as delirium or POCD) is determined by predisposing baseline vulnerabilities and exposure to factors that precipitate poor patient outcomes (such as pain or new medications associated with surgery). In this proposal, we will use a strategy recognizing that baseline vulnerabilities increase geriatric patients risk for poor postoperative cognitive outcomes in conjunction with a disease-oriented focus to minimize the precipitating factors of postoperative delirium and POCD. This strategy is guided by our previous findings demonstrating that postoperative delirium is strongly related to the severity of pain, and probably to the central nervous system effects of opioid analgesics, the usual therapy for postoperative pain. In our framework, the presence of risks for delirium such as advanced age, cognitive impairment, depression, and preoperative medical burden make patients more vulnerable to experiencing adverse effects from the precipitating events of pain and postoperative opioids. The goal of this research is to determine whether an intervention aimed at reducing factors known to precipitate delirium and POCD leads to improvement in postoperative cognitive outcomes in the vulnerable geriatric patients. Based on our pilot study, we found a promising intervention involving the use of an adjunctive non-opioid therapy to reduce postoperative pain and the consumption of opioids, which ultimately resulted in a reduction of the incidence of postoperative delirium. We will conduct a double blind, placebo-controlled study using gabapentin, as an add-on agent in the treatment of postoperative pain in elderly patients undergoing non-cardiac surgery. Our proposed study will test the hypothesis that rates of delirium and POCD can be reduced in those who are vulnerable to experiencing these outcomes through intensive pain management after surgery. Our hypothesis if proven true will contribute not only to a better understanding of the precipitating factors of delirium and POCD and their interactions with baseline vulnerabilities, but will also provide new directions for management of the older surgical patients, hopefully leading to improved functional outcomes and quality of life. Our proposal meets with the major mission of the National Institute of Aging to reduce the burdens of illness and disability in the elderly. PUBLIC HEALTH RELEVANCE: Our proposal aims to investigate the precipitating factors of delirium and POCD and their interactions with baseline vulnerabilities, in order to provide new directions for management of the older surgical patients. Our results will hopefully lead to improved functional outcomes and quality of life of these patients. Our proposal meets with the major mission of the National Institute of Aging to reduce the burden of illness and disability in the elderly.